In order to more precisely define the nature and function of genes controlling the cellular interactions involved in the antibody response and/or Ir genes controlling response to certain soluble antigens, an in vitro system for generating both primary and secondary antibody responses to soluble antigens has been developed and characterized. Responses in the system are T-cell and macrophage dependent, and for TNP-(T,G)-A--L and TNP-(H,G)-A--L are clearly under H-2 linked Ir gene control.